title: Characterization of an intracellular alkaline shift in rat astrocytes triggered by metabotropic glutamate receptors.
abstract: The modulation of intracellular pH by activation of metabotropic glutamate receptors was investigated in cultured and acutely dissociated rat astrocytes. One minute superfusion of 100 microM (1S,3R)-1-aminocyclopentane-1, 3-dicarboxcylic acid (ACPD) evoked an alkaline shift of 0.13 +/- 0. 013 (mean +/- SE) and 0.16 +/- 0.03 pH units in cultured (cortical or cerebellar) and acutely dissociated cortical astrocytes, respectively. Alkalinizations were elicited by concentrations of ACPD as low as 1 muM. The ACPD response was mimicked by S-3-hydroxyphenylglycine (3-HPG) and by (s)-4-carboxy-3-hydroxyphenylglycine (4C-3HPG) but was not blocked by alpha-methyl-4-carboxyphenylglycine (MCPG) or (RS)-1-aminoindan-1, 5-dicarboxcylic acid (AIDA), features consistent with an mGluR5 receptor-mediated mechanism. The ACPD-evoked alkaline shift was insensitive to amiloride, 4,4'-diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS), and the v-type ATPase inhibitors 7-chloro-4-nitrobenz-2-oxa-1,3-diazol (NBD-Cl), bafilomycin, and concanamycin. The alkaline response persisted in Na+- or Cl--free saline, but was reversibly blocked in bicarbonate-free, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solutions. A bicarbonate-dependent and Na+-independent alkaline shift could also be elicited by either 3 mM caffeine or 1 muM ionomycin. These data suggest that a rise in cytosolic Ca2+ activity is instrumental in triggering the alkalinizing mechanism and that this response is independent of the classic depolarization-induced alkalinization mediated by electrogenic sodium-bicarbonate cotransport.
authors.affiliation: Department of Neurosurgery and Department of Physiology and Neuroscience, New York University Medical Center, New York, New York 10016, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Amos
authors.forename: M
authors.initials: M
authors.lastname: Chesler
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D009327:4-Chloro-7-nitrobenzofurazan / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001565:Benzoates / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004024:Dicyclohexylcarbodiimide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006531:HEPES / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007189:Indans / Q000494:pharmacology; D007424:Intracellular Fluid / Q000737:chemistry*; D017136:Ion Transport / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D018942:Macrolides; D009550:Nigericin / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D012964:Sodium / Q000494:pharmacology
chemical_list: C095756:1-aminoindan-1,5-dicarboxylic acid; D000900:Anti-Bacterial Agents; D001565:Benzoates; D002712:Chlorides; D004791:Enzyme Inhibitors; D007189:Indans; D007476:Ionophores; D018942:Macrolides; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C078245:4-carboxy-3-hydroxyphenylglycine; C079694:alpha-methyl-4-carboxyphenylglycine; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D002110:Caffeine; D004024:Dicyclohexylcarbodiimide; D015759:Ionomycin; D000584:Amiloride; C023010:4-hydroxyphenylglycine; C036978:concanamycin A; C040929:bafilomycin A1; D012964:Sodium; D009327:4-Chloro-7-nitrobenzofurazan; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D009550:Nigericin; D006531:HEPES; D002118:Calcium; D005998:Glycine